Oral N-3 PUFAs Attenuate the Neuro-Endocrine Response to Endotoxin in Healthy Subjects

Introduction: The inflammatory syndrome is a frequent condition in critically ill patients. The sequence and interaction of proinflammatory mediators is complex and not yet completely understood. N-3 PUFAs have various non-energetic effects and are supposed to reduce the production of prostaglandines and leukotrienes. Single intravenous bolus injection of endotoxin (LPS) is a model generating a sustained inflammatory response (systemic, metabolic, endocrine changes) in healthy men. By this model we aimed at assessing the immuno-regulating potential of n3-PUFAs in 15 healthy volunteers, randomized to receive (n=7) or not (n=8) a 3-week oral n3-PUFA supplementation.

Methods: Subjects were investigated in a 10h experimental protocol once with 2 ng/kg bacterial LPS i.v. and another time with saline placebo. Systemic parameters (heart rate, temperature, art. blood pressure), indirect calorimetry and blood samples were assessed. Results were analysed by ANOVA for repeated measurements, significance-level p<0.05

Results: Temperature raised simultaneously in both groups at 90min, peaking at 240min after LPS-injection. Fever was significantly lower in n-3 PUFA group from T=240min till the end of the test. As shown in table 1), ACTH- and cortisol-levels (peak at 240min) were also significantly lower in n-3 PUFA group (–25% to –50%, p<0.03). IL-6 and TNF-α did not differ between groups (p=0.3). Heart rate after a peak at 240min was slightly lower in n-3 PUFA group. Resting energy expenditure, plasma glucose, insulin and glucagon did not differ between groups. In the n-3 PUFA group, vascular resistances were 10 to 30% lower and cardiac output was 5 to 20% higher than in control group, but mean arterial pressure was similar in both groups.

Table1: All values for peak at T=240min; mean±SEM

	Temperature (°C)	ACTH (ng/l)	cortisol (nmol/l)	heart rate (b/min)
n-3 PUFA+LPS	38.3±0.16	412±127	750±51	93±4.1
control + LPS	38.5±0.12	808±138	1003±44	97±4.5
placebo control	37.0±0.10	32±7	240±35	64±2.7
p-value	<0.04	<0.03	<10e-3	0.08

Conclusion: These results suggest that n3-PUFAs decrease the neuro-endocrine answer in healthy subjects after i.v. LPS. The energy metabolism (Lipid, glucose turnover, glucagon, insuline) is not affected.